PROJECT SUMMARY The goal of the current study is to examine the effect of aging and systemic inflammation on the concentrations of nucleoside reverse transcriptase inhibitor metabolites within cells, as compared to the endogenous nucleotides they compete with to inhibit HIV viral replication. The study will be conducted using samples taken from HIV+ men ?45 years and ?60 years, who are enrolled in the Multicenter AIDS Cohort Study, and were taking tenofovir disoproxil fumarate and emtricitabine as part of their antiretroviral therapy. First, we will measure the concentrations of the intracellular metabolites and endogenous nucleotides of tenofovir and emtricitabine in stored PBMC samples, and compare the concentrations and ratios of metabolites to the corresponding nucleotides between age groups. Second, we will measure select cytokines in matching plasma and conduct multiple linear regression to ascertain the influence of age and inflammation on the metabolites measured in PBMCs. Ultimately, by advancing our knowledge of the effect of aging on the pharmacology of these agents within HIV+ patients, we can gain insight into how therapy may be adjusted with increasing age to increase efficacy and decrease toxicity.